Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation

doi:10.4049/jimmunol.1601909

CORC > 北京大学 > 生命科学学院

	Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation
	Tao, Jianli ; Zhang, Xiao-Wei ; Jin, Jianshi ; Du, Xiao-Xia ; Lian, Tengfei ; Yang, Jing ; Zhou, Xiang ; Jiang, Zhengfan ; Su, Xiao-Dong
刊名	JOURNAL OF IMMUNOLOGY
	2017
关键词	CYCLIC GMP-AMP CYTOSOLIC DNA SENSOR CGAS INNATE IMMUNITY 2ND-MESSENGER SEQUENCE SYNTHASE ADAPTER PATHWAY STABILITY
DOI	10.4049/jimmunol.1601909
英文摘要	The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders. Upon nonspecific binding of cytosolic B-form DNA, cGAS synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent signaling to produce type I IFNs. The cGAS comprises less conserved N-terminal residues and highly conserved nucleotidyltransferase/Mab21 domains The function and structure of the well-conserved domains have been extensively studied, whereas the physiological function of the N-terminal domain of cGAS is largely uncharacterized. In this study we used a single-molecule technique combined with traditional biochemical and cellular assays to demonstrate that binding of nonspecific dsDNA by the N-terminal domain of cGAS promotes its activation. We have observed that the N terminus of human cGAS (hcGAS-N160) undergoes secondary structural change upon dsDNA binding in solution. Furthermore, we showed that the hcGAS-N160 helps full length hcGAS to expand the binding range on lambda DNA and facilitates its binding efficiency to dsDNA compared with hcGAS without the 160 N-terminal residues (hcGAS-d160). More importantly, hcGAS-N160 endows full length hcGAS relatively higher enzyme activity and stronger activation of STING/IRF3-mediated cytosolic DNA signaling. These findings strongly indicate that the N-terminal domain of cGAS plays an important role in enhancing its function.; National Natural Science Foundation of China [31670740, U1430237, 31270803, 31230023]; Chinese Ministry of Science and Technology [2015CC040097, 2014CB542600, 2014CB910102]; SCI(E); ARTICLE; 9; 3627-3636; 198
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473704]
专题	生命科学学院
推荐引用方式 GB/T 7714	Tao, Jianli,Zhang, Xiao-Wei,Jin, Jianshi,et al. Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation[J]. JOURNAL OF IMMUNOLOGY,2017.
APA	Tao, Jianli.,Zhang, Xiao-Wei.,Jin, Jianshi.,Du, Xiao-Xia.,Lian, Tengfei.,...&Su, Xiao-Dong.(2017).Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation.JOURNAL OF IMMUNOLOGY.
MLA	Tao, Jianli,et al."Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation".JOURNAL OF IMMUNOLOGY (2017).